与高剂量异氟烷相比，右美托咪定与低剂量异氟烷联合麻醉可增加大鼠脑内通过类淋巴途径的溶质转运。
Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane.
作者信息
Benveniste Helene, Lee Hedok, Ding Fengfei, Sun Qian, Al-Bizri Ehab, Makaryus Rany, Probst Stephen, Nedergaard Maiken, Stein Elliot A, Lu Hanbing
机构信息
From the Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut (H.B., H.L.); Center for Translational Neuromedicine, University of Rochester, Rochester, New York (F.D., Q.S., M.N.); Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York (E.A.-B., R.M., S.P.); National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland (E.A.S., H.L.).
出版信息
Anesthesiology. 2017 Dec;127(6):976-988. doi: 10.1097/ALN.0000000000001888.
BACKGROUND
The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not.
METHODS
Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats.
RESULTS
Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats.
CONCLUSIONS
We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.
背景
胶质淋巴通路可使脑脊液在脑内循环，从而促进废物清除。该通路的一个独特之处在于其功能取决于脑的意识状态，并与去甲肾上腺素活性相关。目前的观点认为，所有麻醉药都会通过诱导意识丧失来增加胶质淋巴运输。这种观点意味着，只要麻醉药能诱导意识丧失，其对胶质淋巴运输的影响就应与其作用机制无关。我们通过比较降低去甲肾上腺素的右美托咪定与仅使用异氟醚（不降低去甲肾上腺素）的补充效果来验证这一假设。
方法
将雌性大鼠分别用异氟醚（N = 8）或右美托咪定加低剂量异氟醚（N = 8）麻醉。连续记录生理参数。通过对比增强磁共振成像对胶质淋巴运输进行定量分析。从T1图谱中定量分析脑脊液以及灰质和白质的体积，并从飞行时间磁共振血管造影中提取血管直径。在单独的大鼠组中记录脑电图。
结果
与异氟醚麻醉的大鼠相比，右美托咪定加低剂量异氟醚麻醉的大鼠的胶质淋巴运输增强了32%。在海马体中，与异氟醚麻醉相比，右美托咪定加低剂量异氟醚麻醉期间的胶质淋巴清除效率提高了六倍。两种不同麻醉方案麻醉的大鼠的呼吸和血气状态相当。在右美托咪定加低剂量异氟醚麻醉的大鼠中可观察到纺锤波振荡（9至15赫兹），而异氟醚麻醉的大鼠中则未观察到。
结论
我们认为，麻醉药影响胶质淋巴通路运输不仅是通过诱导意识丧失，还通过其他机制，其中之一是抑制去甲肾上腺素释放。
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